Although a large number of photodimerizable compounds are known today, little information is available on the introduction of photocrosslinking groups into water-soluble host polysaccharides. Technology is known in which photocrosslinked compounds were prepared by introducing various stilbazonium derivatives into the water-soluble polymer polyvinyl alcohol (JP-B-Sho-56-5762, JP-B-Sho-56-54155 and JP-B-Sho-61-12888, the term "JP-B" used herein means examined published Japanese patent application), but the objective of this technology is the immobilization of enzymes and bacteria and, moreover, the host polymers for introduction of photocrosslinking groups are chemically synthesized polymers. In these cases, in order to improve photoreactivity, the photodimerizable compounds are structurally modified to provide variations in absorption of ultraviolet region and its sensitivity.
EP-A-0 554 898 or JP-A-Hei-6-73102 describes a technology in which cinnamic acid is introduced into the natural polymer glycosaminoglycan and the resulting derivative is crosslinked by means of ultraviolet irradiation (the term "JP-A" used herein means unexamined published Japanese patent application). Almost all of the examples given are directed to the preparation of a photocroselinkable glycosaminoglycan compound through the direct introduction of cinnamic acid by way of ester linkage to the hydroxyl group of the host glycosaminoglycan without the use of a spacer group, and the subsequent exposure of the compound to ultraviolet irradiation to provide a photocrosslinked product.
This technology has the disadvantage that cinnamic acid must be introduced at a very high degree of substitution [DS (%): degree of substitution=100.times. (the number of moles of cinnamic acid introduced per repeating constituent saccharide unit)] to a sufficient extent and moreover that the efficiency of the photoreaction is poor. For example, DS necessary for induction of photocrosslinking reaction of a hyaluronic acid derivative incorporated with such photoreactive group (photodimerizable-crosslinkable group) as cinnamoyl group is fairly high (10% or more). In many of said hyaluronic acid derivative, intrinsic properties such as biodegradability, biocompatibility, non-toxicity, non-antigenicity, high swelling, etc. have been lost.
To cause crosslinking reaction of a hyaluronic acid derivative with low DS, it is favorable to use a hyaluronic acid with higher molecular weight. In this case, however, DS of cinnamoyl group is high and thus severe reaction conditions are required in accordance with the method developed previously. It is known that a hyaluronic acid is easily degraded to low molecule by heating, stirring, change of pH, etc. and that this degradation tendency is increased as the molecular weight becomes higher. Namely, the conventional technique accompanies side reactions such as degradation of hyaluronic acid to low molecule. Moreover, the hyaluronic acid derivative with high DS (10% or more) tends to cause stimulation in a living body, possibly damaging the outstanding intrinsic properties of a hyaluronic acid.
The above-described patent application further presents an example in which cinnamic acid was introduced into the carboxyl group of a glycosaminoglycan using a diamine as the spacer but this method is not satisfactory in the selectivity of the cinnamic acid substitution reaction.